This invention relates to bicyclic .beta.-lactam compounds. In particular it relates to a process for preparing fused bicyclic .beta.-lactam 1-carbapenams and 1-carbacephems and to intermediates useful therein.
Many synthetic approaches for the preparation of bicyclic .beta.-lactams have been described. Generally these methods involve the formation of a bicyclic ring system from an appropriately substituted azetidinone ring. One such method involves the treatment of an .alpha.-diazo-.beta.-ketoester substituted azetidinone with rhodium acetate catalyst. For example, an azetidinone substituted in the 4-position by a .alpha.-diazo-.beta.-oxo butan-4-yloic acid methyl ester group [--CH.sub.2 --C(O)--CH(N.sub.2)--COOCH.sub.3 ] and wherein the azetidinone ring nitrogen is unsubstituted results in carbapenam ring formation by the so-called rhodium acetate catalyzed "diazo insertion." This method has been applied to the preparation of the carbapenam ring system such as that of the antibiotic thienamycin, Ratcliffe, R. W.; Salzmann, T. N.; Christensen, B. G., Tetrahedron Lett. 1980, 21, 31, and to the preparation of 1-carbacephems, Evans, D. A.; Sjogren, E. B., Tetrahedron Lett. 1985, 26, 3789. Prior to this invention all such diazo insertion reactions were carried out on the unsubstituted ring nitrogen atom (N--H) resulting in cyclization in varying yields. We have discovered that azetidinones substituted on the ring nitrogen by an alkoxy group or a substituted alkoxy group represented by the general formula ##STR1## wherein n is 1 or 2, undergo facile cyclization with catalytic amounts of rhodium C.sub.2 -C.sub.10 carboxylates e.g. rhodium tetraacetate.
The process of this invention thus provides a route to the bicyclic 1-carbapenams and 1-carbacephems from N-substituted azetidinones obtained from the hydroxamate mediated formation of .beta.-lactams, Miller, M. J., Accts. Chem. Res. 1986, 19, 49; Rajendra, G., Miller, M. J., Tetrahedron Lett., 1987, 28, 6257.